Overview

This is a single-center, single-arm, open-label clinical study to evaluate the efficacy and safety of Adebrelimab plus Apatinib as adjuvant therapy in hepatocellular carcinoma (HCC) patients who are at high risk of recurrence after curative resection.

Eligibility

Inclusion Criteria:

        Participants must meet all of the following conditions in order to be enrolled in this
        study:
          1. Voluntarily participate in this study and sign an informed consent form.
          2. Participants diagnosed with HCC through pathological histology/cytology or clinically
             diagnosed with HCC according to the Diagnosis and Treatment Guidelines for Primary
             Liver Cancer (2024 Edition).
          3. Within 4-12 weeks prior to enrollment, radical resection surgery was performed.
          4. Complete recovery from surgical resection within 4 weeks prior to enrollment.
          5. High risk factors for postoperative recurrence of hepatocellular carcinoma include
             multiple tumors, tumor length>5 cm, poor tumor differentiation (Edmondson III-IV
             grade), margin ≤ 1 cm, invasion of Microvasculature or large vessels, lymph node
             metastasis, sustained abnormalities in AFP or abnormal prothrombin , etc.
          6. Child Pugh liver function rating within 7 days prior to randomization: A or B (≤ 7
             points).
          7. ECOG PS score within 7 days before randomization: 0-1 points.
          8. Have not received systematic anti-tumor treatment for hepatocellular carcinoma in the
             past.
          9. Expected survival time ≥ 12 weeks.
         10. The main organ functions meet the following requirements (within 7 days before
             randomization):
        (1) Blood routine examination: (excluding hemoglobin, no blood transfusion within 14 days
        prior to screening, no use of granulocyte colony-stimulating factor [G-CSF], no medication
        correction):
        • Neutrophil absolute count ≥ 1.5 × 109/L; Platelets ≥ 75 × 10^9/L; • Hemoglobin ≥ 90
        g/L.(Leukocyte and thrombocytopenia caused by splenic hyperfunction can be included in the
        group after partial embolization of the splenic artery or medication correction) (2) Blood
        biochemistry test (no albumin transfusion within 14 days before screening): Serum albumin ≥
        28g/L; Total serum bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; Blood creatinine ≤ 1.5 x
        ULN or Cr clearance rate>50ml/min (3) International standardized ratio (INR) ≤ 2.3 or
        prothrombin time (PT) exceeding the range of normal control ≤ 6 (4) Urinary protein<2+(If
        urinary protein ≥ 2+, 24-hour urine protein quantification is required, and 24-hour urine
        protein quantification<1.0g can be included in the group).
        11. If suffering from hepatitis B virus (HBV) infection, it is necessary to be willing to
        receive antiviral treatment throughout the study period (according to the diagnostic and
        treatment guidelines, such as entecavir) and regularly monitor it; Hepatitis C virus (HCV)
        ribonucleic acid (RNA) positive subjects must receive antiviral treatment according to the
        diagnosis and treatment guidelines, and their liver function must be within CTCAE1 level
        elevation.
        12.Women with fertility: must agree to contraception from the signing of the informed
        consent form until 90 days after the last use of the study drug (whichever is longer). And
        the blood HCG test must be negative within 7 days before starting the study treatment; And
        it must be non lactation period
        Exclusion Criteria:
        If a subject meets any of the following conditions, they will not be allowed to enter this
        study:
          1. Known hepatobiliary carcinoma, sarcoma like hepatocellular carcinoma, combined
             hepatocellular-cholangiocarcinoma，and fibrous layer cell carcinoma; Within 5 years or
             simultaneously suffering from other active malignant tumors other than hepatocellular
             carcinoma (excluding cured skin basal cell carcinoma and cervical carcinoma in situ).
          2. There are uncontrollable extrahepatic metastases, such as lung and brain metastases
             (EHS).
          3. Previously received local treatment, including therapeutic TACE, transarterial
             embolization (TAE), hepatic artery infusion chemotherapy (HAIC), transarterial
             radiation embolization (TARE), etc.
          4. Participants who are preparing to undergo or have previously received organ or
             allogeneic bone marrow transplantation.
          5. Participants who are currently accompanied by interstitial pneumonia or interstitial
             lung disease, or have a history of interstitial pneumonia or interstitial lung disease
             that requires hormone therapy in the past, or other pulmonary fibrosis, organized
             pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia,
             idiopathic pneumonia, or subjects with evidence of active pneumonia or severe lung
             function impairment seen on chest computed tomography (CT) images during screening,
             are allowed to have radiation induced pneumonia in the radiation field; Active
             tuberculosis.
          6. Currently, there is active autoimmune disease or a history of autoimmune disease that
             may recur (including but not limited to: autoimmune hepatitis, interstitial pneumonia,
             uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism,
             hypothyroidism [subjects that can be controlled only through hormone replacement
             therapy can be included]); Subjects with skin diseases that do not need systematic
             treatment, such as vitiligo, psoriasis, alopecia, controlled type I diabetes that
             receive insulin treatment, or childhood asthma that has completely alleviated without
             any intervention after adulthood can be included; Asthma subjects who require medical
             intervention with bronchodilators cannot be included.
          7. Suffering from hypertension and unable to achieve good control through
             antihypertensive drug treatment (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) (based on
             the average BP reading obtained from ≥ 2 measurements), it is allowed to achieve the
             above parameters through the use of antihypertensive therapy; Previously experienced
             hypertensive crisis or hypertensive encephalopathy.
          8. Patients with moderate to severe ascites with clinical symptoms who require
             therapeutic puncture or drainage, or whose Child Pugh score is greater than 7
             (excluding those who only show a small amount of ascites on imaging but do not have
             clinical symptoms); Uncontrolled or moderate to equal amounts of pleural effusion and
             pericardial effusion.
          9. There are clinical symptoms or diseases of the heart that cannot be well controlled,
             such as: (1) According to the standards of the New York Heart Association (NYHA),
             level II or above cardiac insufficiency or cardiac ultrasound examination: LVEF (left
             ventricular ejection fraction)<50%; (2) Unstable angina pectoris; (3) Have experienced
             myocardial infarction within one year prior to the start of the research treatment;
             (4) Clinically significant supraventricular or ventricular arrhythmias require
             treatment or intervention; (5) QTc>480ms (QTc interval is calculated using the
             Fridericia formula; if QTc is abnormal, it can be detected continuously three times
             every 2 minutes, and the average value is taken).
         10. History of spontaneous rupture of liver tumors.
         11. Individuals with a history of hepatic encephalopathy.
         12. Congenital or acquired immune dysfunction in subjects (such as HIV infected
             individuals).
         13. There have been incidents of thrombosis or embolism occurring within the first 6
             months of treatment, such as cerebrovascular accidents (including transient ischemic
             attacks, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.
         14. Patients with a history of gastrointestinal bleeding or a clear tendency towards
             gastrointestinal bleeding within 6 months prior to the start of the study treatment,
             such as those at risk of bleeding or severe esophageal and gastric varices, locally
             active gastrointestinal ulcer lesions, or continuous positive fecal occult blood,
             cannot be included in the study. (If fecal occult blood is positive during the
             baseline period, a follow-up examination is required. If the follow-up examination is
             still positive, gastroduodenoscopy (EGD) is required. If EGD indicates a risk of
             bleeding, esophageal and gastric varices/other gastrointestinal diseases cannot be
             included in the study.)
         15. Within 6 months prior to the start of treatment, there have been abdominal fistulas,
             gastrointestinal perforation, or abdominal abscesses.
         16. Severe, unhealed or cracked wounds, as well as active ulcers or untreated fractures.
         17. Known genetic or acquired bleeding (such as coagulation dysfunction) or thrombotic
             tendencies, such as in hemophilia patients; Currently or recently (within 10 days
             prior to the start of research treatment), full dose oral or injection anticoagulants
             or thrombolytic drugs (prophylactic use of low-dose aspirin, low molecular weight
             heparin allowed) have been used for therapeutic purposes.
         18. Major vascular diseases (such as aortic aneurysm requiring surgical repair or recent
             peripheral arterial thrombosis) occur within 6 months prior to the start of the study
             treatment.
         19. Severe infection within 4 weeks prior to the start of the study treatment, including
             but not limited to hospitalization due to complications of infection, bacteremia, or
             severe pneumonia; Oral or intravenous administration of therapeutic antibiotics within
             2 weeks prior to the start of the study treatment (subjects who receive prophylactic
             antibiotics, such as preventing urinary tract infections or exacerbation of chronic
             obstructive pulmonary disease, are eligible to participate in the study).
         20. It is known that the active ingredients and excipients contained in the
             investigational drugs (Adebelimumab, Apatinib) in this study have hypersensitivity
             reactions, or have a history of severe allergies to any other monoclonal antibodies or
             anti angiogenic targeted drugs.
         21. Use immunosuppressive agents or systemic hormone therapy within 14 days prior to the
             start of the study to achieve immunosuppressive effects (dose>10mg/day prednisone or
             other therapeutic hormones).
         22. Received attenuated live vaccine treatment within 28 days prior to the start of the
             study treatment, or expected to receive such vaccines during the treatment period with
             Adebrelimab or within 60 days after the last dose of Adebrelimab.
         23. Received other experimental drug treatments within 28 days or 5 half-lives (whichever
             is longer) prior to the start of the study treatment.
         24. According to the judgment of the researchers, the subjects may have other factors that
             may affect the research results or cause the study to be terminated midway, such as
             alcoholism, drug abuse, other serious illnesses (including mental illness) that
             require concurrent treatment, serious laboratory test abnormalities, and family or
             social factors that may affect the safety of the subjects.